Warsaw breakage syndrome

Warsaw breakage syndrome (WABS) is an extremely rare autosomal recessive genetic disorder caused by biallelic mutations in the DDX11 gene (also known as ChlR1), which encodes a DNA helicase essential for sister chromatid cohesion and genome stability. The condition was first described in 2010 and is named after the city where the initial patient was identified. WABS shares clinical features with other cohesinopathies and chromosomal breakage syndromes, making differential diagnosis important. The syndrome affects multiple body systems. Key clinical features include severe pre- and postnatal growth retardation (intrauterine growth restriction and short stature), microcephaly, facial dysmorphism (including a small face, upturned nose, and micrognathia), sensorineural hearing loss, and cochlear abnormalities. Affected individuals may also present with intellectual disability of variable severity, abnormal skin pigmentation, cardiac defects, and limb anomalies. A hallmark laboratory finding is increased sister chromatid cohesion defects and sensitivity to mitomycin C, resulting in chromosomal breakage on cytogenetic testing, which overlaps with findings seen in Fanconi anemia. However, unlike Fanconi anemia, patients with WABS typically do not develop bone marrow failure or increased cancer predisposition, though long-term data remain limited due to the rarity of the condition. There is currently no specific or curative treatment for Warsaw breakage syndrome. Management is supportive and multidisciplinary, addressing individual symptoms such as hearing loss (with hearing aids or cochlear implants), developmental delays (through early intervention and educational support), cardiac anomalies (surgical correction if needed), and growth issues. Regular monitoring by a team including geneticists, audiologists, cardiologists, and developmental specialists is recommended. Genetic counseling is important for affected families.

Common questions about Warsaw breakage syndrome